1. MUTATIONS

2. Mutations  errors/changes in the DNA sequence that are inherited.  May have a negative effect, a positive effect, or no effect.

3. Negative Effect  Example: cystic fibrosis  A particular membrane protein (chloride channel) transports chlorine ions between the cell and the extracellular fluid  A mutation in the gene for the protein results in the absence or defective chloride channels

4. Positive effects  Organisms have evolved as a result of mutations that have been naturally selected for.  Example: The large size human brain arose from a series of mutations

5. No effect  Sometimes the mutation doesn’t change the fitness (survival) of an organism.  Ex: Eye colours  Sometimes the side effect of a mutation may not be seen immediately (either later in the lifespan of the organism or in another generation under particular environmental conditions)

6.  Ex: Huntington’s Disease (degenerative nervous system disease) isn’t noticeable until 35-40 years of age.  Viruses: The reason why the influenza virus comes back every year is because it keeps mutating.

7.  Diploid chromosomes have 2 copies of each gene (one on each chromosome – 1 which came from your mom, the other from your dad)  If there is an error in one copy, the other may compensate

8. Types of Mutations  Point Mutations  Chromosomal Mutations

9. POINT MUTATIONS  Mutations at a specific base pair in the genome  Include: silent mutations missence mutations - substitution - deletion - addition/insertion frameshift mutations - deletion - addition/insertion

10. Silent Mutation  Does not result in a change in the amino acid coded for by the mRNA transcript  Therefore, does not cause any visible changes in the organism  Ex: If a mutation occurs in the intron sequence, it will be removed from the mRNA strand before the protein is even translated

11.  Ex: Codes for the amino acid phenylalanine proper mRNA sequence 5’ AGG CUG UUU GGA 3’ mutated sequence 5’ AGG CUG UUC GGA 3’ Still codes for the amino acid phenylalanine  If there is a mistake in the original DNA sequence or in the transcription of the mRNA strand, the mutation may go unnoticed because there is often multiple codons for the same amino acid

12. Missense Mutation  A change in the base sequence that alters a codon, resulting in a different amino acid being placed in the protein chain  Ex: Sickle Cell Anaemia

13. Nonsense Mutation  A change in the base sequence that converts a codon for a particular amino acid into a stop codon.  Therefore, the translation of the protein will stop prematurely  The protein fragment produced from this mutation are shorter than the protein originally coded for and they may be broken down by proteases in the cell  These mutations are often lethal to the cell

14.  Missense and Nonsense mutations may be caused by:  Substitution  Deletion  Insertion

15. Substitution  The replacement of one base in a DNA sequence by another base. (Substitution could also lead to a silent mutation as in the example before)

16. phenylalanine proper mRNA sequence 5’ AGG CUG UUU GGA 3’ mutated sequence 5’ AGG CUG UUA GGA 3’ leucine The “mutant” sequence may make a completely functional protein, a defective protein (but still functional protein), or a completely non-functional protein, Proper mRNA sequence 5’ AGG CUG UUA GGA 3’ mutated sequence 5’ AGG CUG UAA GGA 3’ Missense Mutation Stop codon leucine Nonsense Mutation

17. Deletion  One or more nucleotides is removed from the DNA sequence.

18. Normal mRNA AUG GGA UUC AAC GGA AUA Met - Gly - Phe - Asn - Gly - Ile mRNA with Deletion AUG GAU UCA ACG GAA UA Met – Asn – Leu – Thr - Gln  Creates a drastic change that most likely yields a defective protein

19. Insertion (or Addition)  The addition of an extra nucleotide in the DNA sequence.

20. Normal mRNA AUG GGA UUC AAC GGA AUA Met - Gly - Phe - Asn - Gly - Ile mRNA with Insertion AUG GGA AUU CAA CGG AAU A Met – Gly – Ile – Gln - Arg - Asn -  Creates a drastic change that is most likely yields a defective protein

21. Frameshift Mutations  The previous 2 examples of deletion and insertion resulted in a change to the reading frame called a frameshift mutation.  This drastically changes the protein, causing pretty much every amino acid after the mutation to be incorrect  Therefore, frameshift mutations will most likely create a defective, non-functioning protein

22.  A deletion or insertion of 1 or 2 nucleotides leads to frameshift mutations.  The deletion or insertion of 3 nucleotides does NOT shift the reading frame. It will result in the removal or addition of 1 amino acid only.  This may change the overall protein shape, but may not have as serious an impact as a frame shift mutation

23. What type of mutation? SUBSTITUTION causing a SILENT MUTATION

24. What type of mutation? SUBSTITUTION causing a MISSENSE MUTATION

25. What type of mutation? SUBSTITUTION causing a NONSENSE MUTATION

26. What type of mutation? DELETION causing a FRAMESHIFT MUTATION (and extensive missense mutation)

27. What type of mutation? INSERTION causing a FRAMESHIFT MUTATION (and an immediate NONSENSE MUTATION)

28. What type of mutation? DELETION of 3 nucleotides- no frameshifting

29. Chromosomal Mutations  Mutations of large segments of DNA on the chromosome

30. Recall….  In prophase I of Meiosis, homologous chromosomes pair up and crossing over may occur.

31. TRANSLOCATION  Fragments of DNA from 2 different (nonhomologous chromosomes) exchange places

32. Translocation  Happens when two non-homologous chromosomes interact  Disrupts the normal structure of the genes  When the chromosome is transcribed, the 2 unrelated sequences on a single chromosome will create a new protein with altered function.  Known to cause some types of leukemia

33. Transposable Elements  Happens within one chromosome  “jumping genes”  Fragments of DNA that consistently move from location to location on a chromosome.  If it lands in a coding region of a gene, it will disrupt the transcription of a gene

34. Inversion  The reversal of a segment of DNA within a single chromosome  Genetic material not gained or lost  However, may disrupt a gene sequence.

36. Causes of Mutations  Spontaneous Mutations  Not caused by environmental conditions;  Errors made in DNA replication  ex: accidentally inserting an incorrect base.

37. Causes of Mutations  Induced Mutations  Mutations caused by a chemical agent or radiation  Could lead to certain cancers ie: melanoma (skin cancer) These induced mutations are caused by Mutagenic agents  Agents that can cause a mutation  Ex: UV radiation, X rays, certain chemicals (pesticides)